全文获取类型
收费全文 | 308篇 |
免费 | 23篇 |
出版年
2023年 | 2篇 |
2022年 | 8篇 |
2021年 | 21篇 |
2020年 | 7篇 |
2019年 | 7篇 |
2018年 | 11篇 |
2017年 | 9篇 |
2016年 | 10篇 |
2015年 | 19篇 |
2014年 | 25篇 |
2013年 | 35篇 |
2012年 | 30篇 |
2011年 | 18篇 |
2010年 | 7篇 |
2009年 | 16篇 |
2008年 | 13篇 |
2007年 | 9篇 |
2006年 | 9篇 |
2005年 | 12篇 |
2004年 | 16篇 |
2003年 | 4篇 |
2002年 | 7篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 4篇 |
1996年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1975年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有331条查询结果,搜索用时 15 毫秒
31.
Martinez-Micaelo N González-Abuín N Terra X Richart C Ardèvol A Pinent M Blay M 《The Biochemical journal》2012,441(2):653-663
32.
Keck GE Poudel YB Rudra A Stephens JC Kedei N Lewin NE Blumberg PM 《Bioorganic & medicinal chemistry letters》2012,22(12):4084-4088
The role of the C(8) gem-dimethyl group in the A-ring of bryostatin 1 has been examined through chemical synthesis and biological evaluation of a new analogue. Assays for biological function using U937, K562, and MV4-11 cells as well as the profiles for downregulation of PKC isozymes revealed that the presence of this group is not a critical determinant for the unique pattern of biological activity of bryostatin. 相似文献
33.
CD34+ cord blood cells can be reprogrammed effectively on dishes coated with a synthetic RGD motif polymer (PronectinF?) using a temperature sensitive Sendai virus vector (SeV TS7) carrying reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC. Dish-shaped human ES cell-like colonies emerged in serum-free primate ES cell medium (supplemented with bFGF) in 20% O2 culture conditions. The copy numbers of SeV TS7 vectors in the cytoplasm were drastically reduced by a temperature shift at 38°C for three days. Then, single cells from colonies were seeded on PronectinF?-coated 96-well plates and cultured under na?ve culture conditions (N2B27-based medium supplemented with LIF, forskolin, a MAPK inhibitor, and a GSK inhibitor in 5% O2) for cloning purpose. Dome-shaped mouse ES cell-like colonies from single cells emerged on PronectinF?-coated dishes. These cells were collected and cultured again in primate ES cell medium supplemented with bFGF in 20% O2 and maintained on PronectinF?-coated dishes. Cells were assessed for reprogramming, including the absence of residual SeV and their potential for three germ layer differentiation. Generation of virus-free induced pluripotent stem cell (iPSC) clones from single cells under feeder-free conditions will solve some of the safety concerns related to use of xeno- or allogeneic-material in culture, and contribute to the characterization and the standardization of iPS cells intended for use in a clinical setting. 相似文献
34.
McElroy SJ Hobbs S Kallen M Tejera N Rosen MJ Grishin A Matta P Schneider C Upperman J Ford H Polk DB Weitkamp JH 《PloS one》2012,7(5):e38373
Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC. 相似文献
35.
Manganese activates the mitochondrial apoptotic pathway in rat astrocytes by modulating the expression of proteins of the Bcl-2 family 总被引:1,自引:0,他引:1
Gonzalez LE Juknat AA Venosa AJ Verrengia N Kotler ML 《Neurochemistry international》2008,53(6-8):408-415
Manganese induces the central nervous system injury leading to manganism, by mechanisms not completely understood. Chronic exposure to manganese generates oxidative stress and induces the mitochondrial permeability transition. In the present study, we characterized apoptotic cell death mechanisms associated with manganese toxicity in rat cortical astrocytes and demonstrated that (i) Mn treatment targets the mitochondria and induces mitochondrial membrane depolarization followed by cytochrome c release to the cytoplasm, (ii) Mn induces both effector caspases 3/7 and 6 as well as PARP-1 cleavage and (iii) Mn shifts the balance of cell death/survival of Bcl-2 family proteins to favor the apoptotic demise of astrocytes. Our model system using cortical rat astrocytes treated with Mn would emerge as a good tool for investigations aimed to elucidate the role of apoptosis in manganism. 相似文献
36.
37.
Noemi Čeřovská Tamara Pečenková Tomáš Moravec Jiří Velemínský 《Plant Cell, Tissue and Organ Culture》2004,79(2):147-152
To optimize the efficiency of expression of foreign proteins using Potato virus X (PVX) -- based vector, the gene for the coat protein (CP) of other virus (Potato virus
A, PVA) was cloned into the vector, propagated in E. coli and subsequently inoculated or agroinfected into the host plants. Host range studies showed that the best host plant is N. benthamiana. By means of RT PCR the presence and the stability of the construct were tested. Both ELISA and Western blot analysis were applicable for expressed protein detection. Expression level of PVA CP achieved approximately 5--10 per mille of total soluble proteins. The results demonstrated that agroinfection is the most suitable method for the propagation of our model gene using PVX--based vectors. 相似文献
38.
Elías-Gutiérrez Manuel Smirnov Nikolai N. Suárez-Morales Eduardo Dimas-Flores Noemi 《Hydrobiologia》2001,442(1-3):41-54
Mexico represents a transitional area in which two biogeographic regions meet. A survey of the cladocerans collected in true tropical waterbodies from the country revealed a diverse fauna. The environments examined included temporary pools in the forest, rivers, permanent lagoons and karstic sinkholes. New records or little known taxa include: Diaphanosoma brevireme, D. fluviatile, Pseudosida ramosa, Simocephalus mixtus, Onchobunops tuberculatus,Guernella raphaelis, Chydorus nitidilus, Notoalonacf. globulosa, Alonella brasiliensis and Leydigiopsis curvirostris. In contrast to high altitude systems, with clear nearctic affinity, the lowlands of southeastern Mexico showed a striking resemblance with the South and Central American cladoceran fauna. Apparently, orographic barriers control the distribution of the cladoceran taxa in this region. 相似文献
39.
40.
An imbalance in autophagy contributes to retinal damage in a rat model of oxygen-induced retinopathy
Noemi Anna Pesce Alessio Canovai Flavia Plastino Emma Lardner Anders Kvanta Maurizio Cammalleri Helder André Massimo Dal Monte 《Journal of cellular and molecular medicine》2021,25(22):10480-10493
In retinopathy of prematurity (ROP), the abnormal retinal neovascularization is often accompanied by retinal neuronal dysfunction. Here, a rat model of oxygen-induced retinopathy (OIR), which mimics the ROP disease, was used to investigate changes in the expression of key mediators of autophagy and markers of cell death in the rat retina. In addition, rats were treated from birth to postnatal day 14 and 18 with 3-methyladenine (3-MA), an inhibitor of autophagy. Immunoblot and immunofluorescence analysis demonstrated that autophagic mechanisms are dysregulated in the retina of OIR rats and indicated a possible correlation between autophagy and necroptosis, but not apoptosis. We found that 3-MA acts predominantly by reducing autophagic and necroptotic markers in the OIR retinas, having no effects on apoptotic markers. However, 3-MA does not ameliorate retinal function, which results compromised in this model. Taken together, these results revealed the crucial role of autophagy in retinal cells of OIR rats. Thus, inhibiting autophagy may be viewed as a putative strategy to counteract ROP. 相似文献